- Chirality-Driven Mode of Binding of α-Aminophosphonic Acid-Based Allosteric Inhibitors of the Human Farnesyl Pyrophosphate Synthase (hFPPS)
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Thienopyrimidine-based allosteric inhibitors of the human farnesyl pyrophosphate synthase (hFPPS), characterized by a chiral α-aminophosphonic acid moiety, were synthesized as enantiomerically enriched pairs, and their binding mode was investigated by X-ray crystallography. A general consensus in the binding orientation of all (R)- and (S)-enantiomers was revealed. This finding is a prerequisite for establishing a reliable structure-activity relationship (SAR) model.
- Feng, Yuting,Park, Jaeok,Li, Shi-Guang,Boutin, Rebecca,Viereck, Peter,Schilling, Matthew A.,Berghuis, Albert M.,Tsantrizos, Youla S.
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p. 9691 - 9702
(2019/11/03)
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- Copper-Catalyzed Monoorganylation of Trialkyl Borates with Functionalized Organozinc Pivalates
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Organozinc pivalates, a recently developed air- and moisture-stable organozinc species, were found for the first time as excellent organometallic species in the monoorganylation of trialkyl borates whereby boronic acids were prepared in high yields. The significant advantage of organozinc pivalates over another previously employed organometallic reagents, e. g., organolithium reagents, Grignard reagents and organozinc halides, is that the generation of multiorganylation byproducts such as borinic acids and trialkylboranes were completely suppressed. Additionally, the in situ generated boronates could be directly arranged into Suzuki-Miyaura type cross-coupling reactions to produce biaryls in high yields.
- Fu, Ying,Gou, Bei-Lei,Shi, Chun-Zhao,Du, Zhengyin,Shen, Tong
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p. 4253 - 4257
(2018/09/18)
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- Development of a Concise Multikilogram Synthesis of LPA-1 Antagonist BMS-986020 via a Tandem Borylation-Suzuki Procedure
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The process development for the synthesis of BMS-986020 (1) via a palladium catalyzed tandem borylation/Suzuki reaction is described. Evaluation of conditions culminated in an efficient borylation procedure using tetrahydroxydiboron followed by a tandem Suzuki reaction employing the same commercially available palladium catalyst for both steps. This methodology addressed shortcomings of early synthetic routes and was ultimately used for the multikilogram scale synthesis of the active pharmaceutical ingredient 1. Further evaluation of the borylation reaction showed useful reactivity with a range of substituted aryl bromides and iodides as coupling partners. These findings represent a practical, efficient, mild, and scalable method for borylation.
- Smith, Michael J.,Lawler, Michael J.,Kopp, Nathaniel,McLeod, Douglas D.,Davulcu, Akin H.,Lin, Dong,Katipally, Kishta,Sfouggatakis, Chris
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p. 1859 - 1863
(2017/11/24)
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- Synthesis and evaluation of sulfonamide derivatives as potent Human Uric Acid Transporter 1 (hURAT1) inhibitors
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This letter presents synthesis and structure-activity relationship study of sulfonamide derivatives as inhibitors of Human Uric Acid Transporter 1 (hURAT1). Among all tested sulfonamide derivatives, compounds 9b, 16i and 19b exhibited excellent inhibition activity with IC50 value of 10, 2, and 83?nM, respectively. In addition, compounds 9b and 19b demonstrated moderate PK profile in rats.
- Yang, Xintuo,Pang, Xuehai,Fan, Lei,Li, Xinghai,Chen, Yuanwei
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supporting information
p. 1919 - 1922
(2017/04/10)
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- Scalable, Metal- and Additive-Free, Photoinduced Borylation of Haloarenes and Quaternary Arylammonium Salts
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We report herein a simple, metal- and additive-free, photoinduced borylation of haloarenes, including electron-rich fluoroarenes, as well as arylammonium salts directly to boronic acids. This borylation method has a broad scope and functional group tolerance. We show that it can be further extended to boronic esters and carried out on gram scale as well as under flow conditions.
- Mfuh, Adelphe M.,Doyle, John D.,Chhetri, Bhuwan,Arman, Hadi D.,Larionov, Oleg V.
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supporting information
p. 2985 - 2988
(2016/03/19)
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- Cationic platinum(II) complexes bearing aryl-BIAN ligands: Synthesis and structural and optoelectronic characterization
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Five cationic platinum(II) complexes bearing a 2-(3′-substituted aryl)pyridine cyclometalating ligand (C^N) and a neutral Ar-BIAN ligand have been synthesized: [Pt(ppy)(PhBIAN)]PF6 (1), [Pt(3Fppy)(PhBIAN)]PF6 (2), [Pt(3MeOppy)(PhBIAN)]PF6 (3), [Pt(3MeOppy)(4-FPhBIAN)]PF6 (4), [Pt(ppy)(4-MeOPhBIAN)]PF6 (5). All complexes have been characterized by NMR spectroscopy and mass spectrometry. Complexes 2 and 3 have been characterized by X-ray crystallography. Structure-property relationships were established from UV-visible spectroscopy and cyclic voltammetry studies. Interestingly, we found that when both the C^N and the Aryl-BIAN ligands contained electron-donating MeO groups the absorption spectrum for the platinum complex extended out to 650 nm. The electrochemical studies of these complexes established that they are electronically compatible dye molecules for dye-sensitized solar cells.
- Obrien, Cameron,Wong, Michael Yin,Cordes, David B.,Slawin, Alexandra M. Z.,Zysman-Colman, Eli
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- One-pot cascade approach to phenanthridine-fused quinazoliniminiums from heteroenyne-allenes
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A one-pot cascade method to obtain functionalized phenanthridine-fused quinazoliniminiums from a variety of heteroenyne-allenes is described. This protocol involves formation of C-N and C-C bonds in a single step in the presence of a Lewis acid and trace water to afford pentacyclic title compounds in moderate to good yields.
- Alawode, Olajide E.,Naganaboina, Vijaya Kumar,Liyanage, Thakshila,Desper, John,Rayat, Sundeep
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supporting information
p. 1494 - 1497
(2014/04/03)
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- An easy route to (hetero)arylboronic acids
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An unprecedented spontaneous reactivity between diazonium salts and diboronic acid has been unveiled, leading to a versatile arylboronic acid synthesis directly from (hetero)arylamines. This fast reaction (35 min overall) tolerates a wide range of functional groups and is carried out under very mild conditions. The radical nature of the reaction mechanism has been investigated.
- Erb, William,Hellal, Akila,Albini, Mathieu,Rouden, Jacques,Blanchet, Jerome
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p. 6608 - 6612
(2014/06/09)
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- Mn-catalyzed aromatic C-H alkenylation with terminal alkynes
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The first manganese-catalyzed aromatic C-H alkenylation with terminal alkynes is described. The procedure features an operationally simple catalyst system containing commercially available MnBr(CO)5 and dicyclohexylamine (Cy2NH). The reaction occurs readily in a highly chemo-, regio-, and stereoselective manner delivering anti-Markovnikov E-configured olefins in high yields. Experimental study and DFT calculations reveal that (1) the reaction is initiated by a C-H activation step via the cooperation of manganese and base; (2) manganacycle and alkynylmanganese species are the key reaction intermediates; and (3) the ligand-to-ligand H-transfer and alkynyl-assisted C-H activation are the key steps rendering the reaction catalytic in manganese.
- Zhou, Bingwei,Chen, Hui,Wang, Congyang
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p. 1264 - 1267
(2013/03/14)
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- Highly efficient one-pot access to functionalized arylboronic acids via noncryogenic bromine/magnesium exchanges
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A general and convenient protocol for the electrophilic borylation of aryl Grignard reagents prepared from arylbromides by direct insertion of magnesium in the presence of LiCl or by Mg/Br exchange with iPrMgCl?LiCl has been developed. Various aryl boronic acids were synthesized in a straightforward manner in excellent yields at 0 °C.
- Leermann, Timo,Leroux, Frederic R.,Colobert, Francoise
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supporting information; experimental part
p. 4479 - 4481
(2011/10/09)
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- A recyclable Au(I) catalyst for selective homocoupling of arylboronic acids: Significant enhancement of nano-surface binding for stability and catalytic activity
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Au nanoparticles stabilized by polystyrene-co-polymethacrylic acid microspheres (PS-co-PMAA) were prepared and characterized via X-ray diffraction (XRD), and transmission electron microscope (TEM). The Au nanoparticles supported on the microspheres showed highly selective catalytic activity for homo-coupling reactions of arylboronic acids in a system of aryl-halides and arylboronic acids. X-ray photoelectron spectroscopy (XPS) spectra of the catalyst shows large amounts of Au(l) complexes band to the surface of the Au nanoparticles, which contributes to the selective homocoupling of the arylboronic acids. More importantly, this supported Au complex is a highly recyclable catalyst. The supported Au catalyst can be recycled and reused at least 6 times for a phenylboronic acid reactant, whereas the parent complex shows very low catalytic activity for this compound. The high catalytic activity of this material is attributed to: (1) the high surface to volume ratio which leads to more active sites being exposed to reactants; (2) the strong surface binding of the Au nanoparticle to the Au(1) complexes, which enhances both the stability and the catalytic activity of these complexes. Copyright
- Zhang, Xin,Zhao, Haitao,Wang, Jianhui
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experimental part
p. 5153 - 5160
(2011/12/15)
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- Multiple C-H activations to construct biologically active molecules in a process completely free of organohalogen and organometallic components
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(Chemical Equation Presented) Step by step: Highly selective cross dehydrogenase arylation of acetanilides was developed to construct biaryls under mild condition. With this method, different aryl C-H bonds were activated in sequential reactions to construct functionalized carbazoles (see scheme), which are present as key structural units in various biological molecules and organic optical materials.
- Li, Bi-Jie,Tian, Shi-Liang,Fang, Zhao,Shi, Zhang-Jie
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p. 1115 - 1118
(2008/09/21)
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- Process for preparing boronic and borinic acids
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A process for preparing boronic acids of the formula (I) and borinic acids of the formula (II), by reaction of chloroaromatics of the formula (III) with lithium metal and boron compounds BW′W′W′″, where W′, W′ and W′″ are each, independently of one another, C1-C6-alkoxy, fluorine, chlorine, bromine, iodine, N(C1-C6-alkyl)2 or S(C1-C5-alkyl), in a solvent at temperatures in the range from ?100 to 80° C.
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- (Fluoroorgano)fluoroboranes and -fluoroborates I: Synthesis and spectroscopic characterization of potassium fluoroaryltrifluoroborates and fluoroaryldifluoroboranes
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A convenient preparation of K[ArBF3] (Ar=2-C6H4F, 3-C6H4F, 4-C6H4F, 2,6-C6H3F2, 3,5-C6H3F2, 2,4,6-C6H2F3, 3,4,5-C6H2F3, 2,3,4,5-C6HF4 and C6F5) is offered and the IR and multinuclear NMR spectra of these salts are reported. Treatment of the trifluoroborate salts with BF3 in chlorocarbon solvents provides an easy synthetic route to the corresponding aryldifluoroboranes ArBF2. The multinuclear NMR spectra of ArBF2 are presented. The electron substituent effect of the [-BF3]--group shows this substituent as one of the strongest σ-electron donors, while its π-electron influence is negligible (σI=-0.32, σR=-0.07).
- Frohn,Franke,Fritzen,Bardin
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p. 127 - 135
(2007/10/03)
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- The use of a modified Suzuki reaction for the synthesis of monoarylferrocenes
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A modification of the Suzuki cross-coupling reaction proved to be a clean and useful method for the preparation of monosubstituted arylferrocenes. Iodoferrocene was reacted with a series of substituted arylboronic acids in the presence of sodium carbonate and palladium acetate in aqueous ethanol at room temperature to produce a range of substituted monoarylferrocenes. A systematic investigation undertaken to determine optimal reaction conditions indicated that scrupulous deoxygenation of the solvent is critical. The use of stronger bases such as barium hydroxide and potassium carbonate is favourable and gives rise to better yields of monoarylferrocenes. The reactions also proceed efficiently in aqueous DMF, broadening the scope of the reaction allowing efficient reactions with boronic acids that show low solubility in organic solvents.
- Imrie, Christopher,Loubser, Christa,Engelbrecht, Pieter,McCleland, Cedric W.
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p. 2513 - 2523
(2007/10/03)
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